A 18F-labeled saxitoxin derivative for in vivo PET-MR imaging of voltage-gated sodium channel expression following nerve injury.
A 18F-labeled saxitoxin derivative for in vivo PET-MR imaging of voltage-gated sodium channel expression following nerve injury.
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DOI：
10.1021/ja408300e
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发表时间：
2013-12-04
影响因子：
15
通讯作者：
Du Bois J
中科院分区：
文献类型：
--
作者：
Hoehne A;Behera D;Parsons WH;James ML;Shen B;Borgohain P;Bodapati D;Prabhakar A;Gambhir SS;Yeomans DC;Biswal S;Chin FT;Du Bois J
慢性和神经性疼痛都与周围感觉神经元中某些电压门控钠离子通道（NaV）异构体的表达增加有关。一种对这些通道进行无创成像的方法可能是研究NaV异常表达及其在疼痛发病机制中的作用的有力工具。在此，我们描述了一种针对nav的正电子发射断层扫描（PET）放射性示踪剂的合成和评价，该示踪剂的设计基于有效的nav选择性抑制剂石蜡毒素。损伤大鼠坐骨神经的放射自显像分析和全动物PET-MR成像均表明，全身给药[18F]标记的石蜡毒素衍生物在神经损伤部位集中，与轴切开术后钠通道表达上调一致。这种类型的PET试剂在伤口愈合过程和/或药物治疗后的损伤神经通道表达水平的连续监测中具有潜在的用途。这些信息可能与疼痛行为分析相关，以帮助阐明构成痛觉的复杂分子过程。
Both chronic and neuropathic pain conditions are associated with increased expression of certain voltage-gated sodium ion channel (NaV) isoforms in peripheral sensory neurons. A method for noninvasive imaging of these channels could represent a powerful tool for investigating aberrant expression of NaV and its role in pain pathogenesis. Herein, we describe the synthesis and evaluation of a positron emission tomography (PET) radiotracer targeting NaVs, the design of which is based on the potent, NaV-selective inhibitor saxitoxin. Both autoradiography analysis of sciatic nerves excised from injured rats as well as whole animal PET-MR imaging demonstrate that a systemically administered [18F]-labeled saxitoxin derivative concentrates at the site of nerve injury, consistent with upregulated sodium channel expression following axotomy. This type of PET agent has potential use for serial monitoring of channel expression levels at injured nerves throughout wound healing and/or following drug treatment. Such information may be correlated with pain behavioral analyses to help shed light on the complex molecular processes that underlie pain sensation.
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影响因子：
3
作者：
Elfering, A;Semmer, N;Boos, N
通讯作者：
Boos, N
影响因子：
3.1
作者：
Kiesewetter, DO;Jagoda, EM;Eckelman, WC
通讯作者：
Eckelman, WC
神经元生长因子通过不同的信号转导途径调节两种不同的钠通道类型。
影响因子：
7.8
作者：
D'Arcangelo, G;Paradiso, K;Shepherd, D;Brehm, P;Halegoua, S;Mandel, G
通讯作者：
Mandel, G
影响因子：
6.7
作者：
通讯作者：
--
影响因子：
3.1
作者：
Lee JH;Peters O;Lehmann L;Dence CS;Sharp TL;Carlson KE;Zhou D;Jeyakumar M;Welch MJ;Katzenellenbogen JA
通讯作者：
Katzenellenbogen JA